The instrument requested is a small angle X-ray scattering (SAXS) instrument. The SAXS instrument will be used for investigating the structures of biological macromolecules and their complexes in solution. SAXS provides low (10-20 [unreadable]) resolution information about macromolecular shape, folding, unfolding, aggregation, extended conformations, flexibly linked domains, conformational changes, and assembly state in solution. SAXS data can provide novel insights into biomolecular function that would otherwise not be attainable by other means. For example, there are many cases where individual protein domain structures are known, but the overall assembled state of the entire protein, and how it responds to other molecules, is not known but can be accurately deduced by SAXS. The advantages of SAXS are that it is a solution-based method, so the molecules are not constrained by a crystalline lattice, and there is no size limitation as is the case with NMR. Additionally, SAXS requires much less material than either NMR or X-ray crystallography. The instrument will impact 17 NIH-funded research projects by providing information about molecular shape, domain orientations and conformational changes in solution that are important for molecular function. The NIH funded projects served by the instrument have direct relationship to human health in the areas of: ligand binding to the sweet taste receptor;pre- messenger RNA splicing;binding of ATP to induce subunit movement in the pili of pathogenic bacteria;fatty acid biosynthesis;protein mediated iron-sulfur cluster assembly;interaction of the vitamin D receptor in the presence of medically relevant vitamin D3 analogs;interaction of the cardioviral Leader protein and the RAN GTPase;the HIV-1 frameshift site RNA structure;understanding RNA folding pathways as a function of cellular ions and osmolytes;role of single stranded binding (SSB) protein in genome maintenance;the chaperone Hsp70;the interaction of histone modifying enzymes with their regulatory proteins, and matrix proteins involved in fibronectin and platelet function. Additionally, SAXS data can be used directly in NMR structure determination to improve the quality of NMR structures (NMR-SAXS), which is an emergent technology that extends the frontiers of NMR for determining larger and more accurate structures. ) PUBLIC HEALTH RELEVANCE: The requested instrument will serve 17 NIH funded projects that have direct relationship to human health in the areas of: ligand binding to the sweet taste receptor;pre-messenger RNA splicing;binding of ATP to induce subunit movement in the pili of pathogenic bacteria;fatty acid biosynthesis;protein mediated iron-sulfur cluster assembly;interaction of the vitamin D receptor in the presence of medically relevant vitamin D3 analogs;interaction of the cardioviral Leader protein and the RAN GTPase;the HIV-1 frameshift site RNA structure;understanding RNA folding pathways as a function of cellular ions and osmolytes;role of single stranded binding (SSB) protein in genome maintenance;the chaperone Hsp70;the interaction of histone modifying enzymes with their regulatory proteins, and matrix proteins involved in fibronectin and platelet function. Additionally, SAXS data will be used directly in NMR structure determination in order to extend the frontiers of NMR for determining larger and more accurate structures of biologically important macromolecules.